Novel oral medication for diffuse large B-cell lymphoma! Another indication of XPOVIO®, a first-in-class nuclear export inhibitor, is expected to achieve accelerated approval

Mar 02, 2020View PDF

Antengene’s partner Karyopharm Therapeutics Inc. (Nasdaq: KPTI) announced that the U.S. Food and Drug Administration has accepted for filing its supplemental New Drug Application (sNDA) seeking accelerated approval for XPOVIO® (selinexor), Selective Inhibitor of Nuclear Export (SINE) compound, for the treatment of patients with relapsed or refractory diffuse large B-cell lymphoma (RR DLBCL) who have previously received at least 2-lines treatments. Simultaneously, FDA also included this drug in the Priority Review and assigned a user fee goal date of June 23, 2020 under the Prescription Drug User-Fee Act (PDUFA).

In China, Antengene and Karyopharm formally launched a strategic cooperation in May 2018 to jointly develop four oral innovative medications in clinical and commercial phases, including selinexor. Currently, Antengene is conducting a registered clinical trial of selinexor for relapsed or refractory diffuse large B-cell lymphoma in China. Previously, the indication of selinexor for the treatment of patients with relapsed or refractory multiple myeloma has been granted marketing authorization by the US FDA, and registered clinical studies have been conducted in China. In addition to continuing to advance research and development in the field of hematological and solid tumors, Antengene is establishing a commercial team to actively prepare for the launch of selinexor as well as subsequent products.

“This milestone advance of selinexor means that we have taken an important step toward providing patients and families with oral therapeutic regimens with unique mechanisms of action. Diffuse large B-cell lymphoma is the most common non-Hodgkin’s lymphoma, and as a first-in-class, Selective Inhibitor of Nuclear Export (SINE), for the treatment of relapsed or refractory diffuse large B-cell lymphoma in the world, selinexor has a wide range of clinical value, and thereof, we feel the weight of responsibility and the urgency of time. Antengene will continue to promote the research of selinexor to meet the needs of patients in China and Asia Pacific, and continue to carry forward the spirit of clinical research and development ‘rigorous, scientific, and patient-oriented’ to complete clinical trials with high quality and efficiency. ”

About Selinexor

Selinexor is a first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound. Selinexor functions by selectively binding to and inhibiting the nuclear export protein exportin 1 (XPO1, also called CRM1). Selinexor blocks the nuclear export of tumor suppressor, growth regulatory and anti-inflammatory proteins, leading to accumulation of these proteins in the nucleus and enhancing their anti-cancer activity in the cell. The forced nuclear retention of these proteins can counteract a multitude of the oncogenic pathways that, unchecked, allow cancer cells with severe DNA damage to continue to grow and divide in an unrestrained fashion. In addition to receiving accelerated FDA approval of Selinexor in July 2019 in combination with dexamethasone for the treatment of adult patients with relapsed refractory multiple myeloma (RRMM) who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody.Furthermore, a European Marketing Authorization Application has been submitted to the European Medicines Agency. Selinexor has been granted both Fast Track and Orphan Drug designations by FDA to conduct clinical studies on patients with relapsed or refractory diffuse large B-cell lymphoma who have previously received at least 2-lines treatments. In addition, on February 19, 2020, FDA has included in its accelerated approval a new indication marketing application for the use of selinexor in the treatment of patients with relapsed or refractory diffuse large B-cell lymphoma.

Selinexor is also being evaluated in several other mid-and later-phase clinical trials across multiple cancer indications, including in multiple myeloma in a pivotal, randomized Phase 3 study in combination with Velcade® (bortezomib) and low-dose dexamethasone (BOSTON), as a potential backbone therapy in combination with approved therapies (STOMP), in liposarcoma (SEAL), in recurrent gliomas (KING) and in endometrial cancer (SIENDO), among others.

About Antengene

Antengene is a China-and-U.S. based biopharmaceutical company focusing ondrug discovery, clinical development and the commercialization of innovative therapeutics to meet unmet medical needs.

In April 2017, Celgene(now part of BMS), a global leading innovative biopharmaceutical company became a long-term strategic partner and obtained an equity position in Antengene. In January 2020, former Celgene chairman and CEO Mark J.Alles joins Antengene Board of Directors and former Celgene China GM John Chin joins the company as Chief Business Officer.

Antengene aims to provide the most advanced and first-in-class anti-cancer drugs and other treatments for patients in China/Asia and around the world. Antengene’s pipeline includes six clinical stage products:

ATG-010(selinexor), in combination with the corticosteroid dexamethasone, has been approved by the U.S. Food and Drug Administration, and is currently in registration study in China for the treatment of patients with relapsed or refractory multiple myeloma, and for patients with diffuse large B-cell lymphoma. The drug is also in late clinical development for various other hematologic malignancies and solid tumors. ATG-008, a second-generation dual mTORC1/2 inhibitor, is in a multi-regional clinicaltrial for treatment of hepatocellular carcinoma as well as clinical studies inmultiple other solid tumors. Two other Phase 1 and Phase 2 clinical stagedrugs, ATG-016 and ATG-019, are being studied in multiple cancer types, including colorectal, prostate, NHL, MDS and other solid and hematological malignancies. ATG-527 is being explored for multipleanti-viral indications, including Epstein-Barr virus (EBV) related diseases. ATG-017 is a potent and selective small molecule extracellular signal–regulated kinases 1 and 2 (ERK1/2) inhibitor, in clinical development for multiple solid tumors, NHL and AML. The drug discovery team of Antengene focuses on the development of first-in-class novel molecules with six projects in pre-clinical development, including small molecule, monoclonal and bi-specific antibodies.